Private Selective Sweeps Identified from Next-Generation Pool-Sequencing Reveal Convergent Pathways under Selection in Two Inbred Schistosoma mansoni Strains

BackgroundThe trematode flatworms of the genus Schistosoma, the causative agents of schistosomiasis, are among the most prevalent parasites in humans, affecting more than 200 million people worldwide. In this study, we focused on two well-characterized strains of S. mansoni, to explore signatures of selection. Both strains are highly inbred and exhibit differences in life history traits, in particular in their compatibility with the intermediate host Biomphalaria glabrata.Methodology/Principal FindingsWe performed high throughput sequencing of DNA from pools of individuals of each strain using Illumina technology and identified single nucleotide polymorphisms (SNP) and copy number variations (CNV). In total, 708,898 SNPs were identified and roughly 2,000 CNVs. The SNPs revealed low nucleotide diversity (π = 2×10−4) within each strain and a high differentiation level (Fst = 0.73) between them. Based on a recently developed in-silico approach, we further detected 12 and 19 private (i.e. specific non-overlapping) selective sweeps among the 121 and 151 sweeps found in total for each strain.Conclusions/SignificanceFunctional annotation of transcripts lying in the private selective sweeps revealed specific selection for functions related to parasitic interaction (e.g. cell-cell adhesion or redox reactions). Despite high differentiation between strains, we identified evolutionary convergence of genes related to proteolysis, known as a key virulence factor and a potential target of drug and vaccine development. Our data show that pool-sequencing can be used for the detection of selective sweeps in parasite populations and enables one to identify biological functions under selection.背景 血吸虫属（Schistosoma）的吸虫类扁形动物是血吸虫病的致病病原体，亦是全球范围内最常见的人体寄生虫之一，全球感染人数超2亿。本研究聚焦于两株已被充分表征的曼氏血吸虫（S. mansoni）品系，以探究其选择信号。两品系均为高度近交系，且在生活史性状上存在显著差异，尤其是在与中间宿主光滑双脐螺（Biomphalaria glabrata）的相容性方面。 方法与主要结果 本研究采用Illumina测序技术，对两品系的混合个体DNA开展高通量测序，进而鉴定单核苷酸多态性（SNP）与拷贝数变异（CNV）。共计鉴定得到708,898个SNP以及约2000个CNV。SNP分析显示，各品系内部的核苷酸多样性较低（π=2×10⁻⁴），而两品系间的遗传分化程度较高（Fst=0.73）。基于新近开发的虚拟（in-silico）分析方法，我们进一步在两品系各自鉴定到的总计121和151个选择清除区域中，分别检测到12个和19个品系特异性选择清除区域（即仅该品系拥有、与另一品系无重叠的区域）。 结论与意义 对品系特异性选择清除区域内的转录本进行功能注释后发现，其受到的定向选择与寄生虫-宿主互作相关功能密切相关，例如细胞黏附或氧化还原反应。尽管两品系间遗传分化程度较高，我们仍鉴定到与蛋白水解相关基因的进化趋同现象——这类基因是关键的毒力因子，同时也是药物与疫苗研发的潜在靶点。本研究数据表明，混池测序可用于寄生虫种群的选择清除区域检测，并能够精准鉴定处于选择压力下的生物学功能。